Low spatial structure and selection against secreted virulence factors attenuates pathogenicity in Pseudomonas
Elisa T Granato1,2, Christoph Ziegenhain3,4, Rasmus L Marvig5
1Department of Plant and Microbial Biology, University of Zurich, Zurich, Switzerland. elisa.granato@zoo.ox.ac.uk.
Abstract:
Bacterial opportunistic pathogens are feared for their difficult-to-treat nosocomial infections and for causing morbidity in immunocompromised patients. Here, we study how such a versatile opportunist, Pseudomonas aeruginosa, adapts to conditions inside and outside its model host Caenorhabditis elegans, and use phenotypic and genotypic screens to identify the mechanistic basis of virulence evolution. We found that virulence significantly dropped in unstructured environments both in the presence and absence of the host, but remained unchanged in spatially structured environments. Reduction of virulence was either driven by a substantial decline in the production of siderophores (in treatments without hosts) or toxins and proteases (in treatments with hosts). Whole-genome sequencing of evolved clones revealed positive selection and parallel evolution across replicates, and showed an accumulation of mutations in regulator genes controlling virulence factor expression. Our study identifies the spatial structure of the non-host environment as a key driver of virulence evolution in an opportunistic pathogen.
Insights
Spatial structure significantly impacts Pseudomonas aeruginosa virulence. Virulence dropped in unstructured settings but remained stable in structured environments, revealing key adaptation mechanisms for opportunistic pathogens.
Area of Science:
- Microbiology
- Evolutionary Biology
- Pathogen Dynamics
Background:
- Opportunistic bacterial pathogens like Pseudomonas aeruginosa cause challenging nosocomial infections.
- These pathogens pose risks to immunocompromised individuals, necessitating research into their virulence evolution.
Purpose of the Study:
- To investigate how Pseudomonas aeruginosa adapts its virulence in response to environmental conditions, both with and without its host, Caenorhabditis elegans.
- To identify the genetic and mechanistic basis for virulence evolution in this versatile opportunistic pathogen.
Main Methods:
- Utilized phenotypic and genotypic screening to analyze virulence changes in Pseudomonas aeruginosa.
- Employed whole-genome sequencing to identify genetic mutations and evolutionary patterns in evolved bacterial clones.
- Compared bacterial adaptation in spatially structured versus unstructured environments, with and without the host.
Main Results:
- Bacterial virulence significantly decreased in unstructured environments, irrespective of host presence.
- Virulence remained stable in spatially structured environments.
- Reduced virulence was linked to decreased production of siderophores (without host) or toxins/proteases (with host).
- Genomic analysis revealed parallel evolution and mutations in virulence regulator genes.
Conclusions:
- The spatial structure of the environment is a critical factor influencing the evolution of virulence in opportunistic pathogens.
- Pseudomonas aeruginosa exhibits adaptive strategies that modulate virulence based on environmental complexity and host interaction.
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